The efficacy of Cytomegalovirus (CMV) specific human monoclonal antibodies to both treat and prevent CMV-related disease in immunocompromised patients will be investigated. A Phase 1 dosage, pharmacokinetic and toxicity study using two virus neutralizing human monoclonal antibodies will be conducted, to be followed by larger Phase 2 trial to evaluate their application to the prevention and treatment of CMV disease. Current investigations using CMV-specific monoclonal antibodies to rapidly detect CMV in clinical samples will be expanded to, a) include a large scale prospective trial where the applicability, specificity and sensitivity of immunodiagnosis will be compared to standard virological techniques, and b) a detailed prospective immunopathological analysis of tissue from patients with CMV pneumonia will be performed to better define some basic mechanisms of this disease. To investigate the possibility of specifically directing activated cytotoxic cells to virally infected targets, a series of heteroaggregated antibodies composed of a CMV specific monoclonal antibody covalently linked to an antibody either to the T-3 complex of the T cell or the Fc receptor of the Natural Killer (NK) cell, will be developed. These heteroaggregates will be used to pre- treat T and NK cells derived from the peripheral blood, with the aim of directing them to virus infected targets to cause cell lysis. The specificity of targeting and the efficiency of cytolysis will be defined, and this approach evaluated in vitro as a potential means of treating virus infections.